title: Suppression of tumorigenicity of human prostate carcinoma cells by replacing a mutated RB gene.
abstract: Introduction of a normal retinoblastoma gene (RB) into retinoblastoma cells was previously shown to suppress several aspects of their neoplastic phenotype, including tumorigenicity in nude mice, thereby directly demonstrating a cancer suppression function of RB. To explore the possibility of a similar activity in a common adult tumor, RB expression was examined in three human prostate carcinoma cell lines. One of these, DU145, contained an abnormally small protein translated from an RB messenger RNA transcript that lacked 105 nucleotides encoded by exon 21. To assess the functional consequences of this mutation, normal RB expression was restored in DU145 cells by retrovirus-mediated gene transfer. Cells that maintained stable exogenous RB expression lost their ability to form tumors in nude mice, although their growth rate in culture was apparently unaltered. These results suggest that RB inactivation can play a significant role in the genesis of a common adult neoplasm and that restoration of normal RB-encoded protein in tumors could have clinical utility.
authors.affiliation: Department of Pathology, School of Medicine, University of California, San Diego, La Jolla 92093.
authors.forename: R
authors.initials: R
authors.lastname: Bookstein
authors.forename: J Y
authors.initials: JY
authors.lastname: Shew
authors.forename: P L
authors.initials: PL
authors.lastname: Chen
authors.forename: P
authors.initials: P
authors.lastname: Scully
authors.forename: W H
authors.initials: WH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D012175:Retinoblastoma / Q000235:genetics*; D013489:Suppression, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D004247:DNA